COSMIC-HF - Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure.

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Amgen
Sponsor:
Collaborator:
Cytokinetics
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01786512
First received: January 18, 2013
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

The primary objectives of this study are (i) to select an oral modified release (MR) formulation and dose of omecamtiv mecarbil for chronic twice daily (BID) dosing in subjects with HF and left ventricular systolic dysfunction and (ii) to characterize its pharmacokinetics (PK) over 20 weeks of treatment.


Condition Intervention Phase
Modified Release Oral Formulation
Left Ventricular Systolic Dysfunction
Chronic Heart Failure
History of Chronic Heart Failure
Left Ventricular Ejection Fraction
Pharmacokinetics
Echocardiogram
Drug: Omecamtiv mecarbil
Drug: Placebo
Drug: Omecamtiv Mecarbil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose Escalation Study to Select and Evaluate an Oral Modified Release Formulation of Omecamtiv Mecarbil in Subjects With HF and Left Ventricular Systolic Dysfunction

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Dose Escalation - Characterize Pharmacokinetics - Cmax [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 96, 120 hours after first dose; 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 168 hours following dose on day 7 ] [ Designated as safety issue: Yes ]
    Maximum Observed Plasma Concentration (Cmax)

  • Dose Escalation - Characterize Pharmacokinetics -Cmin [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 96, 120 hours after first dose; 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 168 hours following dose on day 7 ] [ Designated as safety issue: Yes ]
    Minimum Observed Concentration (Cmin)

  • Dose Escalation - Characterize Pharmacokinetics-Tmax [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 96, 120 hours after first dose; 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 168 hours following dose on day 7 ] [ Designated as safety issue: Yes ]
    Time to Reach Maximum Plasma Concentration (Tmax)

  • Dose Escalation - Characterize Pharmacokinetics - AUC12h [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 hours after first dose; 0, 0.5, 1, 2, 3, 4, 6, 8, 12 hours following dose on day 7 ] [ Designated as safety issue: Yes ]
    Area under the curve until 12 hours after investigational product (IP) administration (AUC12h)

  • Dose Expansion - Characterize Pharmacokinetics - Cmax [ Time Frame: predose, predose, 1 , 2, 4, 6, and 8 hours after morning dose on weeks 2 and 12; predose, between 1-4 hours post dose on week 20 ] [ Designated as safety issue: Yes ]
    Maximum Observed Plasma Concentration (Cmax)

  • Dose Expansion - Characterize Pharmacokinetics - Cpredose [ Time Frame: predose before morning dose on Day1, weeks 2, 8 , 12, 16 and 20 ] [ Designated as safety issue: Yes ]
    Concentration prior to IP administration (Cpredose)


Secondary Outcome Measures:
  • Systolic Ejection Time(SET) (msec) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Systolic Ejection Time (SET)

  • Left Ventricular End-Systolic Diameter (LVESD) (cm) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Left Ventricular End-Systolic Diameter (LVESD)

  • Left Ventricular End-Diastolic Diameter (LVEDD) (cm) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Left Ventricular End-Diastolic Diameter (LVEDD)

  • Heart Rate (beats per minute) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in heart rate

  • Stroke Volume (ml) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    Changes from baseline in Stroke Volume

  • Effect of omecamtiv mecarbil on NT-proBNP (pg/mL) [ Time Frame: baseline and 20 weeks ] [ Designated as safety issue: No ]
    To evaluate the effect of 12 weeks of oral dosing with omecamtiv mecarbil on Nterminal pro-B-type natriuretic peptide (NT-proBNP)

  • Dose Escalation - Safety and tolerability of oral omecamtiv mecarbil [ Time Frame: baseline to 35 days ] [ Designated as safety issue: Yes ]
    Subject incidence of adverse events from baseline to 35 days (end of study)

  • Dose Expansion - Safety and tolerability of oral omecamtiv mecarbil [ Time Frame: baseline to 24 weeks ] [ Designated as safety issue: Yes ]
    Subject incidence of adverse events from baseline to week 24 (end of study)


Estimated Enrollment: 570
Study Start Date: February 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Omecamtiv mecarbil Drug: Omecamtiv mecarbil
Oral omecamtiv mecarbil dose of 25-mg BID for 7 days
Other Name: AMG 423
Drug: Omecamtiv mecarbil
Oral omecamtiv mecardbil dose of 50-mg BID for 7 days.
Other Name: AMG 423
Drug: Omecamtiv Mecarbil
Oral omecamtiv mecarbil dose of 25-mg BID for 20 weeks.
Other Name: AMG 423
Drug: Omecamtiv Mecarbil
Oral omecamtiv mecarbil dose of 25 mg BID for 8 weeks followed by 50-mg BID for 12 weeks
Other Name: AMG 423
Placebo Comparator: Placebo Drug: Placebo
Placebo

Detailed Description:

Omecamtiv mecarbil (AMG 423, CK-1827452) is a novel small molecule that increases cardiac contractility by selectively and directly activating the enzymatic domain of cardiac myosin heavy chain, the force-generating motor protein of the cardiac sarcomere. This is a randomized, placebo-controlled, multicenter, phase 2 study, consisting of a dose escalation phase to select 1 of 3 omecamtiv mecarbil oral formulations in 2 dose escalation cohorts, followed by an expansion phase to evaluate 20 weeks of administration of the selected omecamtiv mecarbil formulation at 2 target dose levels, compared with placebo.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • History of chronic HF, defined as requiring treatment for HF for a minimum of 4 weeks prior to screening
  • Treated with stable, optimal pharmacological therapy for ≥ 4 weeks
  • History of left ventricular ejection fraction (LVEF) ≤ 40%
  • Elevated N-terminal fragment BNP (NT-proBNP)

Exclusion criteria:

  • Severe uncorrected valvular heart disease
  • Hospitalization within 30 days prior to enrollment
  • Hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease
  • Acute Myocardial Infarction, Unstable angina or persistent angina at rest within 30 days prior to randomization
  • Systolic BP > 160 mmHg or < 90 mmHg or diastolic BP > 90 mmHg
  • TBL ≥ 2x ULN; AST or ALT ≥ 3x ULN
  • Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01786512

Contacts
Contact: Amgen Call Center 866-572-6436

  Show 100 Study Locations
Sponsors and Collaborators
Amgen
Cytokinetics
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01786512     History of Changes
Other Study ID Numbers: 20110151
Study First Received: January 18, 2013
Last Updated: July 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
Pharmacokinetics
Omecamtiv mecarbil
AMG 423
Double-blind
Randomized
Placebo-controlled
Oral forumlation
CK-1827452
Cardiac myosin activator

Additional relevant MeSH terms:
Heart Failure
Ventricular Dysfunction, Left
Heart Diseases
Cardiovascular Diseases
Ventricular Dysfunction

ClinicalTrials.gov processed this record on July 29, 2014